1. Field of the Invention
The present invention relates to compounds capable of forming complexes with lanthanides, to the complexes obtained and to the uses thereof.
2. Description of the Related Art
The present invention relates to compounds capable of forming complexes with lanthanides, to the complexes obtained and to the uses thereof.
Radioactive markers have been widely used in the field of medical imaging and immunology. On account of the drawbacks of these markers, they have largely been replaced with fluorescent markers.
However, the use of fluorescent markers presents a number of drawbacks, especially due to the auto-fluorescence of the biological media studied and to the scattering of light in the machines. Lanthanide ion complexes have been proposed to allow a time-resolved acquisition that eliminates these drawbacks. In order to be used as a time-resolved luminescent marker, a lanthanide ion complex must have numerous characteristics, the most important of which are hydrophilicity, stability in water, the presence of chromophores capable of generating the antenna effect (Sabbatini, N. et al. Coord. Chem. Rev. 1990, 123, 201), good photophysical properties (high absorption, excitation over a readily accessible energy range, long lifetime of the excited state and high luminescence quantum yield) and a reactive function that allows covalent grafting.
The compounds currently proposed rarely combine all of these criteria. For example, the first complexes developed by the company Wallac Oy under the name Delfia Chelate (Hemmilä, I. et al. Anal. Biochem. 1984, 137, 335) do not have good photophysical properties and it is necessary to perform a lanthanide extraction step in order to measure its luminescence. The compounds developed by CIS Bio International are cryptates, which require the use of fluoride anions in order to increase the luminescence (Hemmilä, I. et al. Drug Discovery Today, 1997, 2, 373). The stability of the compounds also poses serious problems. Thus, the compounds developed by CyberFluor under the name BCPDA only form stable luminescent complexes at high concentrations (Marriott, G. et al., Biophysical Journal, 1994, 67, 957).
Lanthanide complexes, especially of gadolinium, have been used as relaxation agents or contrast agents for NMR medical imaging (Caravan, P. et al. Chem. Rev. 1999, 99, 2293). This use is permitted due to the fact that the first coordination sphere of the lanthanide is not fully saturated with the ligand in aqueous solution, water molecules thus being able to complete the coordination sphere.